Fungicidal pyridyl sulfenyl carbamates

ABSTRACT

Novel fungicidal pyridyl sulfenyl carbamates having the formula ##STR1## wherein R is selected from the group consisting of haloalkyl, C 1  -C 8  alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, alkanoyl, alkylamino, arylamino, arylalkylamino and substituted pyridylcarbamoyl; 
     R 1  is C 1  -C 3  alkoxy or C 1  -C 3  haloalkoxy or halomethoxy; alkenyloxy; and halogen; 
     R 2  is C 1  -C 3  alkyl; 
     X is oxygen or sulfur; and 
     Y is oxygen or sulfur 
     and fungicidally acceptable organic and inorganic salts thereof which are highly effective fungicides for use both as preventive and curative fungicides are disclosed herein.

This is a divisional of application Ser. No. 114,811, filed Oct. 29,1987, now U.S. Pat. No. 4,800,205, issued Jan. 24, 1989.

BACKGROUND OF THE INVENTION

Fungal infection of crops such as barley, rice, tomatoes, wheat, beans,roses, grapes and other agriculturally important crops can cause heavylosses in both quantity and quality of agricultural products. It istherefore extremely desirable to have means of preventing, controllingor eliminating fungal growth. Much preventive spraying with commercialfungicides is conducted to attempt to prevent the establishment andgrowth of fungi on agriculturally important crops. It would also bedesirable to have a curative fungicide which, on detection of fungalinfestation, could destroy the fungi and eliminate the deleteriouseffects by use of a post-infection curative spray.

SUMMARY OF THE INVENTION

Novel fungicidal pyridyl sulfenyl carbamates having the formula ##STR2##wherein R is selected from the group consisting of haloalkyl, preferablyC₁ -C₃ haloalkyl; C₁ -C₈ alkyl; aryl; substituted aryl; arylalkyl;substituted arylalkyl; alkanoyl, preferably C₁ -C₄ alkanoyl; alkylamino,arylamino, arylalkylamino and substituted pyridyl carboxamidoyl;

R₁ is C₁ -C₃ alkoxy or C₁ -C₃ haloalkoxy, preferably methoxy; orhalomethoxy; alkenyloxy; and halogen wherein the halogen is chlorine,bromine or fluorine;

R₂ is C₁ -C₃ alkyl, preferably methyl;

X is oxygen or sulfur; and

Y is oxygen or sulfur

and fungicidally acceptable organic and inorganic salts thereof whichare highly effective fungicides for use both as preventive and curativefungicides are disclosed herein.

The term "fungicide" is used to mean a compound which controls fungalgrowth. "Controls" includes prevention, destruction and inhibition offungal growth. The term "curative" is meant to refer to a post-infectionapplication of a fungicide which establishes control of fungal infectionand prevents development of deleterious effects of the fungi on the hostcrop.

DETAILED DESCRIPTION

The novel fungicidal compounds of this invention are fungicidal pyridylsulfenyl carbamates having the general formula ##STR3## wherein R isselected from the group consisting of haloalkyl, preferably C₁ -C₃haloalkyl, C₁ -C₈ alkyl, aryl, substituted aryl, arylalkyl wherein thepreferred aryl is phenyl, the alkyl is C₁ -C₃ alkyl and the preferredsubstitutions are Cl, Br, F and nitro, alkanoyl, preferably C₁ -C₄alkanoyl, alkylamino, arylamino, arylalkylamino, and substitutedpyridylcarboxamidoyl, R₁ is C₁ -C₃ alkoxy or C₁ -C₃ haloalkoxypreferably methoxy or halomethoxy, alkenyloxy and halogen wherein thehalogen is chlorine, bromine or fluorine, R₂ is C₁ -C₃ alkyl, preferablymethyl, X is oxygen or sulfur, Y is oxygen or sulfur and fungicidallyacceptable organic and inorganic salts thereof which are highlyeffective fungicides for use both as preventive and curative fungicidesare disclosed herein.

The compounds of this invention can be generally prepared by a two-stepreaction process. The first step comprises reacting the appropriateaminopyridine with the appropriate chloroformate in an inert solventsuch as dichloromethane in a suitable reactor. It is desirable tomaintain an acid scavenger such as pyridine in the reaction vessel. Thereaction generally will proceed at room temperature but will operate ata temperature range from -30° to 80° C. The reaction should go tocompletion within 1 to 3 hours. The resulting product is recovered in aconventional manner by washing with an alkali solution such as sodiumhydroxide and water, drying over conventional drying agents such asmagnesium sulfate and crystallizing from hexane. The resulting carbamateis then reacted with a properly substituted sulfenyl chloride in aninert solvent in the presence of a tertiary amine such as pyridine ortriethylamine, or inorganic base such as sodium hydride (NaH). Salts ofthe various sulfenylpyridyl carbamates can be conventionally prepared byreacting at least a molar amount of a Lewis acid with the carboxamide.Preferably the reaction is run in a solvent for the carboxamide. Theprepared salt is recovered from the reaction mixture by conventionaltechniques.

Pyridyl sulfenyl carbamates of the invention are basic. The unprotectednitrogen atom of the pyridyl ring can be protonated by an acid, eitherorganic or inorganic. Representative inorganic acids are hydrochloric,nitric, hydrobromic, sulfuric, sulfamic and phosphoric. Representativeorganic acids are acetic, trifluoroacetic, benzoic, benzenesulfonic,p-toluenesulfonic, naphthalenesulfonic, phenylphosphonic andorganophosphonic. The salts so formed are also fungicidal.

EXAMPLE 1 Preparation of O-methyl-N-(2-methoxy-5-pyridyl)-carbamate

5-Amino-2-methoxy pyridine (8.0 grams, 0.064 moles) was dissolved inmethylene chloride (100 ml) followed by addition of pyridine (9.5 g,0.12 mol). To this solution was added methyl chloroformate (8.3 g, 0.088mol) dropwise with stirring at approximately 15° C. The addition wasexothermic and the reaction was stirred for a further two hours at roomtemperature. It was then washed with water (2 times), dried overmagnesium sulfate, filtered, and evaporated in vacuo to yield an orangesolid that was triturated with hexane several times to yield 9.3 g, m.p.100°-101° C. of the title compound as identified by its infrared (IR),nuclear magnetic resonance (NMR) spectra and by mass spectroscopic (MS)analysis. This product was used as an intermediate to produce the novelcompounds of Examples 2-4.

EXAMPLE 2 Preparation ofMethyl-N-(benzylmethylaminosulfenyl)-N-(2-methoxy-5-pyridyl)-carbamate

O-Methyl-N-(2-methoxy-5-pyridyl)-carbamate (5.0 g, 0.027 mol) was addedin portions to a stirred mixture of sodium hydride (0.7 g, 0.027 mol)suspended in a solution of tetrahydrofuran (100 ml) anddimethylsulfoxide (10 ml). There was a moderate exotherm and a gas wasevolved. The reaction solution was cooled to -65° C. andbenzylmethylamino sulfenyl chloride (5.1 g, 0.027 mol) was slowly added.The temperature was allowed to rise to room temperature. The mixture wasdiluted with water (200 ml) and extracted with methylene chloride (100ml). This extract was washed with saturated sodium chloride solution,dried over anhydrous magnesium sulfate, filtered and evaporated in vacuoto give 8.8 g of crude product. This was extracted with hexane and flashchromatographed on florisil to give 2.0 g of the title product as anoil, n_(D3) ⁰ 1.5460.

EXAMPLE 3 Preparation ofO-Methyl-N-trichloromethanesulfenyl-N-(2-methoxy-5-pyridyl)-carbamate

O-Methyl-N-(2-methoxy-5-pyridyl)-carbamate (5.0 g, 0.027 moles) wasadded in portions to a stirred mixture of sodium hydride (0.7 g, 0.027mol) in dry tetrahydrofuran (80 ml). Hydrogen gas was evolved. After 30minutes, the stirred suspension was cooled to -50° C. andtrichloromethanesulfenyl chloride (5.0 g, 0.027 mol) dissolved in drytetrahydofuran (5 ml) was added slowly. At the completion of theaddition, cooling was discontinued and the mixture was allowed to cometo room temperature. The reaction mixture was stirred for 2 hours atroom temperature and diluted with methylene chloride (150 ml) and washedwith brine (2×100 ml), dried over magnesium sulfate, filtered andevaporated in vacuo to yield 7.7 g of crude product. This was furtherpurified by extraction with hexane and filtration through a bed offlorisil, giving 2.1 g of the title product, m.p. 48.0°-55.0° C.

EXAMPLE 4 Preparation of SulfenylN,N'-bis-[O-methyl-N-(2-methoxy-5-pyridyl)-carbamate]

O-Methyl-N-(2-methoxy-5-pyridyl)-carbamate (5.0 g, 0.027 mol) was addedportion-wise to a stirred suspension of sodium hydride (0.7 g, 0.027mole) in dry tetrahydrofuran (100 ml) at room temperature. This reactionmixture was cooled to -50° C. and sulfur dichloride (2.8 g, 0.027 mol)was added with stirring. Cooling was discontinued and the temperatureallowed to rise to room temperature and stirred for 90 minutes. Thereaction was diluted with methylene chloride (100 ml) and washed withwater (100 ml) and brine (100 ml). The organic phase was dried overmagnesium sulfate, filtered and evaporated in vacuo to give 5.2 grams ofa viscous oil which solidifed on trituration with hexane to give 3.9 gof the title product, m.p. 89°-94° C.

Representative compounds of this invention and their properties areshown in Table I.

                                      TABLE I                                     __________________________________________________________________________     ##STR4##                                                                                                     Physical Properties                           Cmpd.                           Melting Point                                 No. R             R.sub.1                                                                            R.sub.2                                                                            X Y n.sub.D.sup.30 or RF                          __________________________________________________________________________    1   CCl.sub.3     OCH.sub.3                                                                          CH.sub.3                                                                           O O 48.0-55.0° C.                               ##STR5##     OCH.sub.3                                                                          CH.sub.3                                                                           O O 49.0-55.0° C.                          3   CCl.sub.3     Cl   CH.sub.3                                                                           O S solid                                         4   CCl.sub.3     Cl   CH.sub.3                                                                           O O 57.0-60.0° C.                          5                                                                                  ##STR6##     OCH.sub.3                                                                          CH.sub.3                                                                           O O 90.0-95.0° C.                          6                                                                                  ##STR7##     OCH.sub.3                                                                          CH.sub.3                                                                           O O 120.0-123.0° C.                        7   N(C.sub.4 H.sub. 9).sub.2                                                                   OCH.sub.3                                                                          CH.sub.3                                                                           O O 1.5129                                        8                                                                                  ##STR8##     OCH.sub.3                                                                          CH.sub.3                                                                           O O 89.0-94.0° C.                          9                                                                                  ##STR9##     OCH.sub.3                                                                          CH.sub.3                                                                           O O 1.5460                                        __________________________________________________________________________

EXAMPLE 5 Preventative Spray Evaluation Procedures Barley Powdery Mildew(BPM)

Northrup King Sunbar 401 barley seed is planted (12 seeds/2" pot) in asandy-loam soil seven days prior to testing. The test compound isdiluted in a 50/50 acetone/water solution to produce concentrationsdecreasing from 750 ug/ml. The test solution is then sprayed onto thebarley plants with atomizing sprayers.

Twenty-four hours later, test plants are placed in an inoculation boxequipped with a circulating fan. Barley plants with heavily sporulatingErysiphe graminis lesions are placed in front of the fan to dislodge anddistribute the spores. After two minutes the fan is shut off and thechamber is left closed five minutes for the spores to settle. Inoculatedplants are then placed on an automatic sub-irrigation greenhouse bench.

Results are recorded seven days following inoculation as percent diseasecontrol based on the percent reduction in infected area as compared tothe untreated control plants. Compound concentrations which provide 90%disease control (EC 90) are determined from dosage/dilution curves.

Leaf Rust (LR)

Seven seeds of Anza wheat are planted in 2" pots in a sandy-loam soil 12days prior to testing. The compound to be tested is diluted with a 50/50acetone/water solution to produce concentrations decreasing from 750ug/ml. Twelve ml of test solution are sprayed onto the wheat plants withan atomizing sprayer.

A suspension of Puccinia recondita urediospores is prepared by vacuumingspores from wheat leaves with ureida pustules and suspending 10⁵spores/ml in deionized water plus 0.5% Tween® 20 (polyoxyethylenesorbitan monolaurate). Plants are inoculated 24 hours after treatment byspraying with the spore suspension to run-off, allowing it to dry on theleaves, respraying to runoff, and then placing the plants into a mistchamber. Following 48 hours in the mist, plants are moved to asubirrigation greenhouse bench.

Results are recorded ten days following inoculation as percent diseasecontrol based on the percent reduction in lesion area as compared to theuntreated control plants. Compound concentrations which provide 90%disease control (EC 90) are determined from dosage/dilution curves.

Botrytis Blight (BB)

Two white rose petals are placed in a petri dish lined with wet filterpaper. The compound to be tested is diluted with a 50/50 acetone/watersolution to produce concentrations decreasing from 750 ug/ml. One halfml of test solution is atomized onto the petals and allowed to dry.

Inoculum is prepared by adding a 5 mm plug from a two-week old Botrytiscinerea culture grown on Elliot's V-8 agar, to 10 ml sterile distilledwater plus 0.5 ml grape juice. A 20 ul drop of this inoculum suspensionis placed on each petal. Petri dishes with inoculated petals are storedin sealed plastic boxes to maintain saturated humidity.

Results are read four days following inoculation as a percent reductionin necrotic area compared to the acetone/water controls. Compoundconcentrations which provide 90% disease control (EC 90) are determinedfrom dosage/dilution curves.

The results are presented in Table II as an approximate EC 90 in partsper million. 750 ppm equals 750 ug/ml. Partial control at 750 ppm (lessthan 90%) is indicated by (750). An asterisk (*) indicates no control at750 ppm.

                  TABLE II                                                        ______________________________________                                        Cmpd. No.     BPM        LR      BB                                           ______________________________________                                        1             *          *        80                                          2             *          *        50                                          3             (750)      750     *                                            4             (750)      750     *                                            5             (750)      (750)   250                                          6             (750)      *       250                                          7             (750)      *       150                                          8             (750)      (750)    80                                          9             (750)      (750)   250                                          ______________________________________                                    

The compounds of the present invention are useful as fungicides,especially as preventative or curative fungicides, and can be applied ina variety of ways at various concentrations. In general, these compoundsand formulations of these compounds can be applied directly to the cropfoliage, the soil in which the crop is growing or in the irrigationwater for the crop or soil. In practice, the compounds herein definedare formulated into fungicidal compositions, by admixture, infungicidally effective amounts, with the adjuvants and carriers normallyemployed for facilitating the dispersion of active ingredients foragricultural applications, recognizing the fact that the formulation andmode of application of a toxicant may affect the activity of thematerials in a given application. Thus, these active fungicidalcompounds may be formulated as wettable powders, as emulsifiableconcentrates, as powdery dusts, as solutions or as any of several otherknown types of formulations, depending upon the desired mode ofapplication. Preferred formulations for preventative or curativefungicidal applications are wettable powders and emulsifiableconcentrates. These formulations may contain as little as about 0.1% toas much as about 95% or more by weight of active ingredient. Afungicidally effective amount depends upon the nature of the seeds orplants to be treated and the rate of application varies from about 0.05to approximately 25 pounds per acre, preferably from about 0.1 to about10 pounds per acre.

Wettable powders are in the form of finely divided particles whichdisperse readily in water or other dispersants. The wettable powder isultimately applied to the plants either as a dry dust or as a dispersionin water or other liquid. Typical carriers for wettable powders includeFuller's earth, kaolin clays, silicas and other readily wet organic orinorganic diluents. Wettable powders normally are prepared to containabout 5% to about 95% of the active ingredient and usually also containa small amount of wetting, dispersing, or emulsifying agent tofacilitate wetting and dispersion.

Dry flowables or water dispersible granules are agglomerated wettablepowders made by either pan granulation or by fluidized bed. The dryflowable is ultimately applied to the plants as a dispersion in water orother liquid. These granules are dust-free and free flowing when dry andyet upon dilution in water, form homogeneous dispersions. Typicalcarriers for dry flowables include fuller's earth, kaolin clays, silicasand other readily wet organic or inorganic diluents. The dry flowablesnormally are prepared to contain from about 5% to about 95% of theactive ingredient and usually contain a small amount of wetting,dispersing or emulsifying agent to facilitate wetting and dispersion.

Emulsifiable concentrates are homogeneous liquid compositions which aredispersible in water or other dispersant, and may consist entirely ofthe active compound with a liquid or solid emulsifying agent, or mayalso contain a liquid carrier, such as xylene, heavy aromatic naphtha,isophorone and other non-volatile organic solvents. For fungicidalapplication, these concentrates are dispersed in water or other liquidcarrier and normally applied as a spray to the area to be treated. Thepercentage by weight of the essential active ingredient may varyaccording to the manner in which the composition is to be applied, butin general comprises about 0.1% to 95% of active ingredient by weight ofthe fungicidal composition.

Typical wetting, dispersing or emulsifying agents used in agriculturalformulations include, for example, the alkyl and alkylaryl sulfonatesand sulfates and their sodium salts; polyhydroxy alcohols; and othertypes of surface-active agents, many of which are available in commerce.The surface-active agent, when used, normally comprises from 0.1% to 15%by weight of the fungicidal composition.

Dusts, which are free-flowing admixtures of the active ingredient withfinely divided solids such as talc, clays, flours and other organic andinorganic solids which act as dispersants and carriers for the toxicant,are useful formulations for many applications.

Pastes, which are homogeneous suspensions of a finely divided solidtoxicant in a liquid carrier such as water or oil, are employed forspecific purposes. These formulations normally contain about 5% to about95% of active ingredient by weight, and may also contain small amountsof a wetting, dispersing or emulsifying agent to facilitate dispersion.For application, the pastes are normally diluted and applied as a sprayto the area to be affected.

    ______________________________________                                        EXAMPLES OF TYPICAL FORMULATIONS                                              ______________________________________                                        Oil                                                                           Ingredient            Weight %                                                ______________________________________                                        Compound 1             1                                                      Oil solvent-heavy aromatic naphtha                                                                  99                                                      Total                 100                                                     Emulsifiable Concentrate                                                      Compound 1            50                                                      Kerosene              45                                                      Emulsifiying agent (mixture of long                                                                  5                                                      chain ethoxylated polyethers with                                             long chain sulfonate)                                                         Total                 100                                                     Emulsifiable Concentrate                                                      Compound 1            90                                                      Kerosene               5                                                      Emulsifying agent (mixture of long                                                                   5                                                      chain ethoxylated polyethers with                                             long chain sulfonate)                                                         Total                 100                                                     ______________________________________                                        Dusts and/or Powders                                                          Ingredient        Wt. %    Wt. %    Wt. %                                     ______________________________________                                        Compound 1        0.5      50.0     90.0                                      Attapulgite Clay Powder                                                                         93.5     44.0     4.0                                       Sodium lignin sulfonate                                                                         5.0      5.0      5.0                                       Sodium dioctyl sulfosuccinate                                                                   1.0      1.0      1.0                                       Total             100.0    100.0    100.0                                     ______________________________________                                    

Other useful formulations for fungicidal applications include simplesolutions of the active ingredient in a dispersant in which it iscompletely soluble at the desired concentration, such as acetone,alkylated naphthalenes, xylene and other organic solvents. Pressurizedsprays, typically aerosols, wherein the active ingredient is dispersedin finely divided form as a result of vaporization of a low boilingdispersant solvent carrier, such as the Freons, may also be used.

The fungicidal compositions of this invention are applied to the plantsin the conventional manner. Thus, the dust and liquid compositions canbe applied to the plant by the use of power-dusters, boom and handsprayers and spray dusters. The compositions can also be applied fromairplanes as a dust or a spray because they are effective in lowdosages.

We claim:
 1. A compound having the structural formula ##STR10## whereinR is ##STR11## R₁ is selected from the group consisting of C₁ -C₃alkoxy, C₁ -C₃ haloalkoxy and halogen;R₂ is C₁ -C₃ alkyl; X is oxygen orsulfur; and Y is oxygen or sulfuror a fungicidally acceptable organic orinorganic salt thereof.
 2. The compound of claim 1 wherein R₁ is --OCH₃,R₂ is --CH₃, X is 0 and Y is
 0. 3. A fungicidal composition comprising afungicidally effective amount of a compound having the structuralformula ##STR12## where R is ##STR13## R₁ is selected from the groupconsisting of C₁ -C₃ alkoxy, C₁ -C₃ haloalkoxy and halogen;R₂ is C₁ -C₃alkyl; X is oxygen or sulfur; and Y is oxygen or sulfuror a fungicidallyacceptable organic or inorganic salt thereof in admixture with a diluentor carrier therefor.
 4. The method of controlling fungi comprisingapplying to the area where control is desired a fungicidally effectiveamount of a compound having the formula ##STR14## where R is ##STR15##R₁ is selected from the group consisting of C₁ -C₃ alkoxy, C₁ -C₃haloalkoxy and halogen;R₂ is C₁ -C₃ alkyl; X is oxygen or sulfur; and Yis oxygen or sulfur or a fungicidally acceptable organic or inorganicsalt thereof.
 5. The method of claim 4 wherein R₁ is --OCH₃, R₂ is--CH₃, X is 0 and Y is 0.